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很多药物(特别是抗癌药物)是通过抑制靶细胞内DNA的生物合成而发挥疗效的。为了阐明这一类型药物作用的分子机制,首先应区分作用方式是属于损伤DNA模板型还是干扰代谢型。一般说来,DNA的损伤作用近乎不可逆;干扰代谢的作用绝大多数具有可逆性,一旦药物作用被解除,细胞内DNA合成即可逐渐复原。根据这一原理,可利用肿瘤细胞体外解除药物作用后~3H-TdR掺入(代表DNA合成)的图谱(以下称掺入曲线)来测定药物的作用方式。
Many drugs (especially anti-cancer drugs) work by inhibiting the biosynthesis of DNA in target cells. To elucidate the molecular mechanism of the effects of this type of drug, one should first distinguish whether the mode of action is a damaging DNA template or an interfering metabolite. In general, DNA damage is almost irreversible; most of the role of interference with the reversible metabolism, once the drug is lifted, the DNA synthesis can be gradually restored. According to this principle, we can make use of the map of 3H-TdR incorporation (representing DNA synthesis) after the tumor cells in vitro drug release (hereinafter referred to as the incorporation curve) to determine the mode of action of the drug.